The applicants are members of a multidisciplinary team whose long-term objective is to enhance the value of laser therapy for atherosclerotic disease by increasing scientific understanding of laser-tissue interactions. The research already completed suggest that certain laser capabilities may extend the clinical value of laser therapy beyond its currently limited role. The proposed project seeks to develop these promising findings obtained during NHLBI R01 support from 1987 to 1990, and during new studies conducted since relocation in 1990 to the Harvard Medical School. It will focus on the preliminary findings that lasers can remove arterial stenoses leaving a less thrombogenic surface and vasoconstrictive artery than balloon angioplasty, and that lasers may facilitate localized gene therapy to block cell proliferation and restenosis. Specific Aim 1 is to define the parameters of laser tissue interaction in vascular tissue by evaluating thermal and mechanical events which influence thrombogenicity. An AV shunt model will be used to assess acute thrombogencity in dogs and chronic thrombogenicity in atherosclerotic rabbits. This will be measured as the amount of platelet deposition and thrombus formation at laser and balloon treated sites. Supplemental anti- thrombotic regimes will also be tested. Specific Aim 2 is to determine in atherosclerotic rabbits if lasing creates less vasoconstriction than balloon angioplasty. Vasomotor response to nitorprusside, bradykinin norepinephrine, acetylcholine, serotonin and vasopressin will be determined. Successful completion of the proposed project will provide an objective assessment of these potential unique capabilities of lasers to alter vascular biologic and physiologic behavior. If these capabilities are substantiated, their exploitation in laser systems designed for clinical use could lead to realization of the currently unfulfilled promise of laser therapy.